PMID- 29163025
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 1662-5099 (Print)
IS  - 1662-5099 (Electronic)
IS  - 1662-5099 (Linking)
VI  - 10
DP  - 2017
TI  - BDNF/trkB Induction of Calcium Transients through Ca(v)2.2 Calcium Channels in 
      Motoneurons Corresponds to F-actin Assembly and Growth Cone Formation on beta2-Chain 
      Laminin (221).
PG  - 346
LID - 10.3389/fnmol.2017.00346 [doi]
LID - 346
AB  - Spontaneous Ca(2+) transients and actin dynamics in primary motoneurons 
      correspond to cellular differentiation such as axon elongation and growth cone 
      formation. Brain-derived neurotrophic factor (BDNF) and its receptor trkB support 
      both motoneuron survival and synaptic differentiation. However, in motoneurons 
      effects of BDNF/trkB signaling on spontaneous Ca(2+) influx and actin dynamics at 
      axonal growth cones are not fully unraveled. In our study we addressed the 
      question how neurotrophic factor signaling corresponds to cell autonomous 
      excitability and growth cone formation. Primary motoneurons from mouse embryos 
      were cultured on the synapse specific, beta2-chain containing laminin isoform (221) 
      regulating axon elongation through spontaneous Ca(2+) transients that are in turn 
      induced by enhanced clustering of N-type specific voltage-gated Ca(2+) channels 
      (Ca(v)2.2) in axonal growth cones. TrkB-deficient (trkBTK(-/-)) mouse motoneurons 
      which express no full-length trkB receptor and wildtype motoneurons cultured 
      without BDNF exhibited reduced spontaneous Ca(2+) transients that corresponded to 
      altered axon elongation and defects in growth cone morphology which was 
      accompanied by changes in the local actin cytoskeleton. Vice versa, the acute 
      application of BDNF resulted in the induction of spontaneous Ca(2+) transients 
      and Ca(v)2.2 clustering in motor growth cones, as well as the activation of trkB 
      downstream signaling cascades which promoted the stabilization of beta-actin via the 
      LIM kinase pathway and phosphorylation of profilin at Tyr129. Finally, we 
      identified a mutual regulation of neuronal excitability and actin dynamics in 
      axonal growth cones of embryonic motoneurons cultured on laminin-221/211. 
      Impaired excitability resulted in dysregulated axon extension and local actin 
      cytoskeleton, whereas upon beta-actin knockdown Ca(v)2.2 clustering was affected. We 
      conclude from our data that in embryonic motoneurons BDNF/trkB signaling 
      contributes to axon elongation and growth cone formation through changes in the 
      local actin cytoskeleton accompanied by increased Ca(v)2.2 clustering and local 
      calcium transients. These findings may help to explore cellular mechanisms which 
      might be dysregulated during maturation of embryonic motoneurons leading to 
      motoneuron disease.
FAU - Dombert, Benjamin
AU  - Dombert B
AD  - Institute of Clinical Neurobiology, University of Wuerzburg, Wuerzburg, Germany.
FAU - Balk, Stefanie
AU  - Balk S
AD  - Institute of Clinical Neurobiology, University of Wuerzburg, Wuerzburg, Germany.
FAU - Luningschror, Patrick
AU  - Luningschror P
AD  - Institute of Clinical Neurobiology, University of Wuerzburg, Wuerzburg, Germany.
FAU - Moradi, Mehri
AU  - Moradi M
AD  - Institute of Clinical Neurobiology, University of Wuerzburg, Wuerzburg, Germany.
FAU - Sivadasan, Rajeeve
AU  - Sivadasan R
AD  - Institute of Clinical Neurobiology, University of Wuerzburg, Wuerzburg, Germany.
FAU - Saal-Bauernschubert, Lena
AU  - Saal-Bauernschubert L
AD  - Institute of Clinical Neurobiology, University of Wuerzburg, Wuerzburg, Germany.
FAU - Jablonka, Sibylle
AU  - Jablonka S
AD  - Institute of Clinical Neurobiology, University of Wuerzburg, Wuerzburg, Germany.
LA  - eng
PT  - Journal Article
DEP - 20171030
PL  - Switzerland
TA  - Front Mol Neurosci
JT  - Frontiers in molecular neuroscience
JID - 101477914
PMC - PMC5670157
OTO - NOTNLM
OT  - BDNF
OT  - Cav2.2
OT  - F-actin
OT  - growth cone
OT  - motor axon
OT  - trkB
EDAT- 2017/11/23 06:00
MHDA- 2017/11/23 06:01
PMCR- 2017/01/01
CRDT- 2017/11/23 06:00
PHST- 2017/08/08 00:00 [received]
PHST- 2017/10/12 00:00 [accepted]
PHST- 2017/11/23 06:00 [entrez]
PHST- 2017/11/23 06:00 [pubmed]
PHST- 2017/11/23 06:01 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 10.3389/fnmol.2017.00346 [doi]
PST - epublish
SO  - Front Mol Neurosci. 2017 Oct 30;10:346. doi: 10.3389/fnmol.2017.00346. 
      eCollection 2017.